中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (1): 127-128.doi: 10.4103/1673-5374.286969

• 观点:脑损伤修复保护与再生 • 上一篇    下一篇

肌苷:一种坐骨神经损伤的新疗法

  

  • 出版日期:2021-01-15 发布日期:2020-11-26

Inosine: a novel treatment for sciatic nerve injury

Fellipe Soares dos Santos Cardoso, Ana Maria Blanco Martinez, Fernanda Martins de Almeida*   

  1. Laboratório de Neurodegeneração e Reparo – Departamento de Anatomia Patológica – Hospital Universitário Clementino Fraga Filho HUCFF/Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (Soares dos Santos Cardoso F, Blanco Martinez AM, Martins de Almeida F)
    Instituto de Ciências Biomédicas – ICB/Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (Martins de Almeida F)
  • Online:2021-01-15 Published:2020-11-26
  • Contact: Fernanda Martins de Almeida, MD, PhD, fealmeida.maia@gmail.com.

摘要: https://orcid.org/0000-0002-0821-5730 (Ana Maria Blanco Martinez)

Abstract: Trauma to the peripheral nervous system often results in loss of motor and sensory functions of the affected area of the body, leading to a series of functional impairments (Allodi et al., 2012). Injuries to peripheral nerves initiate a series of complex events, known as Wallerian degeneration, which allows the injured axons to regenerate and reinnervate their targets (Allodi et al., 2012). Damage to a nerve induces multiple alterations, which include: axonal degeneration, breakdown of myelin sheath, Schwann cells (SC) proliferation and conversion to a repair phenotype which express cytokines and chemokines that allow the infiltration and activation of macrophages (Mietto et al., 2015; Jessen and Mirsky, 2016). Then, both macrophages and SC clean up axon and myelin debris, and promote in the distal degenerated portion of the axon, a favorable microenvironment that is required for regeneration. After clearance, SC forms the bands of Büngner, which will guide the regenerating axons to the target and will allow the reestablishment of new synapses with the muscle, followed by the process of axon remyelination (Allodi et al., 2012; Jessen and Mirsky, 2016). Concomitant with these events, the neuronal cell body turns into a pro-regenerative state, allowing the injured axons to grow. Some positive signals such as cyclic adenosine monophosphate (cAMP) increase and the entrance of extracellular Ca2+ to the axoplasm can trigger and maintain the pro-regenerative state. cAMP has a key role in the growth state of the neuronal soma, regulating axon attraction or repulsion by guidance cues from the environment. One example is the nerve growth factor and brain-derived neurotrophic factor. Low levels of cAMP turn the attractive effects of these neurotrophic factors, important for axonal growth, in repulsion. Moreover, these signals activate a cascade of mitogen-activated protein kinases, which induces the expression of transcriptions factors such as activating transcription factor 3 and signal transducers and activators of transcription, increasing the expression of neurotrophic factors, growth proteins such as growth associated protein-43, cytoskeleton proteins and extracellular matrix components (Allodi et al., 2012).